Three days of CIV rh-Endostatin in combination with PD-1 antibody plus chemotherapy as first-line regimen for EGFR/ALK-negative, advanced or metastatic, non-squamous non–small cell lung cancer (NSCLC): A open label, multicenter, phase II and cohort study (ENPOWER).
Authors: Dong Wang, Yan Feng, Yuju Bai, Hu Ma, Li Huang, Tienian Zhu, Haihong Qian, Yanping Li, Xinjian Fang, Biyong Ren
Journal: Journal of Clinical Oncology (2022)

9031 Background: rh-Endostatin, an antiangiogenic agent, in combination with chemotherapy is recommended by the CSCO guideline as the first-line treatment for EGFR/ALK-negative, advanced or metastatic, non-squamous non–small-cell lung cancer (NSCLC). However, evidence supporting the application of rh-Endostatin plus PD-1 antibody in clinical settings has been limited. The ENPOWER study is an open-label, multicenter, phase II and cohort study to evaluate the efficacy and safety of three days of continuous intravenous infusion (CIV) of rh-Endostatin in combination with PD-1 antibody plus chemotherapy as the first-line regimen for EGFR/ALK-negative, advanced or metastatic, non-squamous NSCLC. Methods: ENPOWER was an open label, multicenter, phase II and cohort study. Patients with EGFR/ALK-negative, advanced or metastatic, non-squamous NSCLC were enrolled and assigned into the following two cohorts. Patients in Cohort 1 (PD-1 combination) received rh-Endostatin plus PD-1 antibody plus standard chemotherapy (Carboplatin or Cisplatin plus Pemetrexed) during the induction period up to 4 - 6 cycles and rh-Endostatin plus PD-1 antibody during the maintenance period until disease progression or intolerable adverse events. Those in cohort 2 different from in cohort 1 was not subject to PD-1 antibody. Results: 43 subjects were evaluable for efficacy analysis, with 15 in Cohort 1 (PD-1 combination) and 28 in Cohort 2. ORR and DCR was 53% and 93% in Cohort 1 (CR, 0; PR, 8; SD, 6; PD,1) and 39% and 86% in Cohort 2 (CR 0; PR 11; SD, 13; PD, 4), respectively. 50 subjects were included in safety analysis. The overall incidence of AEs of any grade was 89%. 92% of the patients in the cohort 1 and 85% in the cohort 2. The majority of AEs was grade 1 or 2. Adverse events of any grade that occurred in at least 10% of patients were neutropenia（76%），nausea/vomiting (61%), AST/ALT abnormal (33%), palpitate (28%), anemia (22%) and skin hypersensitivity (11%) in the cohort 1 and neutropenia（68%），nausea/vomiting (59%), AST/ALT abnormal (21%), palpitate (16%), anemia (40%) in the cohort 2, respectively. Adverse events of grade 3 or higher found in the cohort 1 were neutropenia (23%) and those were neutropenia (19%), AST/ALT abnormal (3%) and anemia (3%) in the cohort 2. Seemingly, Adverse events that occurred more frequently in the cohort 1 than in the cohort 2 were AST/ALT abnormal, palpitate and skin hypersensitivity. Conclusions: Three days of CIV rh-Endostatin in combination with PD-1 antibody plus chemotherapy for the first line treatment of EGFR/ALK negative, advanced or metastatic, non-squamous NSCLC could obtain the better improvement in the efficacy and result in the higher frequent in some of AEs. Clinical trial information: NCT: 04063449.